Sarin antidotes

Nerve Agent Antidote Kit (NAAK or MARK I) consists of an atropine auto-injector (2 mg), a pralidoxime chloride auto-injector (2-Pam-Cl, 600 mg), the plastic clip joining the two injectors, and a foam case. The kit serve as a countermeasure to nerve agents, including tabun (GA), sarin (GB), soman (GD), GF, and VX. Military personnel can receive three MARK I for self/buddy aid. Possible side effects of atropine and/or 2-PAM-C1 are deemed insignificant in a nerve agent casualty. Intravenous atropine and 2-PAM-C1 can also be made available. The MARK I kit is manufactured by Survival Technology, Inc., Rockville, Maryland. 

Dr. Aghajanian also tried the nerve agent GB (sarin) as a possible antidote. It worked quite well, as did VX, another well-known lethal nerve agent. He and Dr. Sidell sueeessfully used both drugs to reverse EA 3580 intoxieation. If not for the general publie fear of anything to do with nerve gas, one might reeommend sarin or VX as superior antidotes to use in the treatment of dmg-indueed delirium. 

In Japan, a number of years ago, a terrorist attack with sarin killed a dozen individuals confined to a subway car out of roughly a thousand people in the nearby vicinity. Sarin has little effect on the skin, due to rapid evaporation. It is true that the Iraqis killed many Kurds with nerve gas, but the victims were unprepared, had no training, no detection devices, no masks or other protection, no antidote and no practical way to avoid the gas. None of these vulnerabilities would be the case in a conflict with American troops. 

The pX a (6.5-8.2) and nucleophilicity of MINA, 44, and of a series of aliphatic oximes derived from it, were found to be consistent with their ability to reactivate AChE inhibited by the nerve agents, sarin and VX. Yet, despite their ability to significantly reactivate AChE in the brains of sarin-intoxicated rats, these aliphatic oximes are not used as antidotes for treatment of OP poisoning in humans this is presumably due to their poor stability in aqueous solution and to their rapid clearance from the circulation. 

Loomis, T.A., Salafsky, B. 1963. Antidotal action of pyrldl-nium oximes in anticholinesterase poisoning comparative effects of soman, sarin, and neostigmine on neuromuscular function. 

Today, everyone is aware of terrorist activity. A well-known terrorist attack involving chemicals occurred in 1995 with the release of the nerve gas sarin in the subway systems of Tokyo, resulting in the death of 12 people and injury of many more. Should chemicals again be used for terrorist activity, forensic pharmacologists and toxicologists may be called upon to analyze bodily samples in order to identify the chemical, determine its mechanism of action, and propose antidotes and preventive measures. 

List two antidotes used to treat sarin gas poisoning. 

The presence of sarin, soman, and VX in the brain demonstrates the necessity for antidotes, especially AChE reactivators, to be capable of passing the blood-brain barrier, representing a current scientific challenge (Lorke et al, 2008 Okuno et al, 2008). 

Ohta, H., Ohmori, T., Suzuki, S., Ikegaya, H., Sakurada, K., Takatori, T. (2006). New safe method for preparation of sarin-exposed human erythrocytes acetylcholinesterase using non-toxic and stable sarin analogue isopropyl p-nitrophenyl methylphosphonate and its application to evaluation of nerve agent antidotes. Pharm. Res. 23 2827-33. 

Sadly, chemical warfare weapons are dangerous instruments of terror. Two recent episodes in which sarin was used by terrorists in Japan cast a cloud over attempts to control the use of these weapons. Sarin was released in a residential area of the city of Matsumoto on June 27, 1994, and in a crowded Tokyo subway less than a year later, on March 20, 1995. In Matsumoto, about 600 residents and rescuers were affected and seven died. More than 5500 people were poisoned and 12 died in the Tokyo incident. Many more might have perished if it were not for the quick action and bravery of firemen, police, and others and the availability of antidotes in Japanese hospitals. (Two subway attendants died removing containers of sarin from subway cars.)... 

FIGURE 10.1 Effectiveness of galantamine/atropine as an antidote against the acute toxicity and lethality of 1.5 X LD50 soman or sarin in guinea pigs. Note that there is no need for additional supportive therapy. (From Albuquerque, E.X. et al., Proc. Natl. Acad. Sci. USA, 103, 13220, 2006. With permission.)... 

L35. Loomis, T. A., Welsh, M. J., Jr., and Miller, G. T., A comparative study of some pyridinium oximes as reactivators of phosphorylated acetylcholinesterase and as antidotes in sarin poisoning. Toxicol. Appl. Pharmacol. 5, 588-598 (1963). 

Application of well-known chemical agents in terrorist acts as complex compositions with other compounds may significantly to hamper their identification in the air and on the ground with use of usual analytical methods. In this case we can expect that clinical course of intoxication of victims will be atypical and curing effect of known antidotes and other medications will be brought to nothing. Practical confirmation of such application of chemical agent in terrorist purposes with use of sarin took place in Japan (Matsumoto, 1994 Tokyo Subway, 1995). 

Efficacy of the anticonvulsant usage in antidotic formulas depends considerably on OPC type. Thus, index of protection (IP) for the composition of ChR (HI-6 inclusive), cholinolytics and diazepam is much higher for the treatment of intoxication with soman and tabun, than in poisonings with sarin and VX [93],... 

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